Previously, drugs for treatment of the cornea and anterior chamber of the eye have been applied by topical administration. This drug delivery technique is disadvantageous because it does not allow the drug to be dispensed in a continuous manner. The drug administered in the conjunctival sac is rapidly diluted by the tear fluid and repeated administration of the drug is required to make up for the loss.
Ophthalmic drugs may also be administered systemically. This method of administration also has the disadvantage that the drug reaches the desired concentration in the cornea and anterior chamber for only a short period of time, after which the drug is cleared from the circulation. Repeated application of a drug through systemic administration may produce undesired systemic toxicity.
In other medical areas, such as chemotherapy, the use of polymers for the slow release of drugs has been reported. The use of glycolide and lactide for slow release of chemotherapeutic agents has been reported previously by Sinclair (Proceedings of the Fifth International Symposium on Controlled Release of Bioactive Materials, Akron, Ohio, University of Akron Press, 1987); the use of bioactive oligomer microspheres containing anti-cancer agents has been reported in the Journal of Bioactive and Compatible Polymers (3:126, 1988); and the use of ethylene-vinyl acetate has been reported in Langer et al. Methods in Enzymology 12:399, 1985.
U.S. Pat. No. 3,960,150 to Hussain et al. discloses devices for the controlled continuous administration of a predetermined dosage of a drug to the eye including a device where the drug is confined in microcapsule reservoirs dispersed through a bioerodible matrix. The device is adapted for insertion in the sac of the eye bounded by the surfaces of the bulbar conjunctiva of the sclera of the eyeball and the palpebral conjunctiva of the lid. Such a device has the disadvantage with respect to drug delivery to the cornea that it does not allow a direct delivery of a drug to the cornea of the eye. Instead, the drug reaches the cornea only after dilution in the tear film.
Recently, it was found that hydrophilic plastic or collagen made in the form of a contact lens and placed on the cornea can enhance healing after corneal transplantation or other forms of corneal surgery such as refractive surgery. Collagen corneal shields have been developed as bandages to protect and promote the healing of the cornea. Collagen corneal shields are commonly stored in a dehydrated condition and are rehydrated before they are placed on the eye. When placed on the eye, the shields absorb ocular fluids and conform to the shape of the cornea. They then slowly dissolve, thereby lubricating the eye and promoting healing of the cornea.
It has also been found that hydrophilic contact lenses or corneal shields prolong the contact between drugs and the cornea and allow greater penetration of drugs into the anterior chamber of the eye. A lens or shield may serve as a drug delivery vehicle for topical administration of drugs by absorbing and slowly releasing topically applied drugs. Further, a collagen corneal shield may be soaked in a solution of a drug during rehydration so that the shield absorbs the drug. When the shield is applied to the cornea, the drug gradually permeates through the collagen shield toward the cornea and is released slowly and continuously as the collagen shield dissolves.
Recently, drug delivery systems using contact lenses made of hydrophilic plastic and collagen cornea shields have been tested in animals and humans as a means of providing a slow-release delivery of drugs to the cornea and anterior chamber. O'Brien et al. (Journal of Cataract and Refractive Surgery 14:505-507) reported a comparison of therapeutic soft contact lenses and collagen shields for administration of tobramycin to the cornea. Their results showed an enhanced penetration of tobramycin when delivered by corneal collagen shields. Similarly, Sawusch et al. (ARVO Abstracts; Invest Ophthalmol Vis Sci Suppl 29:228, 1988) reported successful treatment of bacterial keratitis with the use of collagen shields. In another study, Unterman et al. (Journal of Cataract and Refractive Surgery 14:500-504, 1988) reported therapeutic concentrations of tobramycin in the cornea and aqueous humor of rabbits up to eight hours after application of collagen shields containing the antibiotic. Further studies by Hobden et al. (Archives of Ophthalmology 106:1605-1607, 1988) showed the efficacy of tobramycin-soaked collagen shields in the treatment of Pseudomonas keratitis in rabbits; similar results were seen after 4 hours of treatment, compared to topical application of the drug every 30 minutes. Replacement of the dissolving antibiotic-soaked collagen shield with a new one provided further therapeutic effects similar to the effects achieved with repeated topical application of the drug. A study by Poland et al. (Journal of Cataract and Refractive Surgery 14:489-491, 1988) showed that collagen shields rehydrated in 4% tobramycin were well-tolerated clinically in the eyes of patients after corneal surgery and patients with nonsurgical epithelial healing problems.
The disadvantage of the use of the collagen shield alone as a drug delivery system is that the concentration of the drug that can be absorbed directly by the collagen shield is limited. Because of this, in order to achieve a sustained drug concentration over a long period of time, either the drug must be applied topically over a collagen shield that is in place on the eye, or collagen shields must be replaced regularly with new collagen shields hydrated in the drug. Both methods are therefore inconvenient, require monitoring of the patient, and involve a risk of patient noncompliance. Further, the use of the collagen shield as a direct drug delivery system is limited to water-soluble drugs, because lipid-soluble substances generally do not permeate the collagen shield.
Accordingly, there exists the need for a method and apparatus for slow release drug delivery of a high concentration of a drug directly to the cornea and anterior chamber of an eye over a long period of time. Further, there exists a need for a drug delivery system that allows either water-soluble or lipid-soluble drugs to be delivered to the cornea and anterior chamber. Further, it is desirable to have a drug delivery system that comprises substances that are not toxic to the eye.